1.0. Field of the Invention
The present invention relates to optical imaging of tissues and, more particularly, to a light detection and ranging (LIDAR) system for medical diagnostics particularly suited for detecting the presence of inhomogeneities in tissues, such as tumors.
2.0. Description of the Related Art
The noninvasive and early detection of biological tissue abnormalities with submillimeter dimensions, such as cancerous tumors, is an important challenge and constant improvements are being sought. The well-established X-ray and ultrasound techniques lack the resolution to detect such small objects some of which may be cancerous tumors. In addition, the risk of tissue ionization that may damage healthy tissues prevents the use of X-rays for routine examination. Magnetic resonance imaging (MRI) has submillimeter resolution, but the cost of this technique is still high for general use.
The need for a safe, inexpensive, and efficient method for the early detection of tissue imperfections, such as cancerous tumors, has led to the investigation of optical imaging techniques. For such applications, light between 600 and 1300 nm that falls within a transmission window is minimally absorbed as it propagates through tissue and can therefore be used to non-invasively probe internal structures in search of tissue abnormalities. The existence of this transmission window, combined with the highly forward directed scattering of light, allows for substantial penetration of light in tissue in search of tumors. The main disadvantage of using optical light inside the body is that light is highly scattered by tissue. This optical scattering degrades an image in several different ways. First, some light that does not reach the object, such as the cancerous tumor, is disadvantageously reflected by intervening particles of the tissue itself into the receiver field of view. This backscattered, diffuse light creates a background noise level that degrades the image contrast. Secondly, light that reaches and is reflected from the object encounters small forward angle scattering on its travel back to the receiver and is commonly referred to as snake photons or snake light. These snake photons limit the photon detection and degrade contrast by decreasing the image sharpness or resolution.
Unlike photon limited detection, contrast limited detection cannot be improved simply by increasing the transmitted optical power (or the detector quantum efficiency). However, a method for separating the unscattered or minimally scattered, ballistic or snake photons from the diffuse photons that have been scattered several times could be used to improve object detection and imaging. These improvements may be further described with reference to FIG. 1 composed of FIGS. 1(A), 1(B) and 1(C) illustrating the three most popular approaches for accomplishing this task of improving object detection and imaging and which are a time domain (FIG. 1(A)) approach, a coherence domain (FIG. 1(B)) approach, and a frequency domain (FIG. 1(C)) approach. It is important to note that the approaches depicted in FIG. 1 and FIG. 2, to be described hereinafter, are shown for a transmission type measurement (i.e., the light is transmitted from one side of the tissue and light is detected from the other side of the tissue) to simplify the explanation. These techniques can also be used in a reflection type measurement (i.e., the light is transmitted from one side of the tissue and light is detected from the same side of the tissue).
FIG. 1, as well as FIG. 2, is illustrated in three sections, one section 10 showing the parameters related to transmitting a light signal into the tissue 16 under examination, a second section 12 showing the parameters associated with the signals detected at the other side of the tissue 16, and a third section 14 showing the parameters associated with the signals detected at the other side of the tissue 16 and the measurements performed on these signals. The second section 12 also includes the inhomogeneity 18, such as a cancerous tumor, in the tissue, and a waveform 20 that illustrates a composite scattered signal comprised of the ballistic light 22 that passes straight through the object 18, the snake light 24, and the diffuse light 26.
The time domain approach (FIG. 1(A)) transmits a light pulse 28, in the direction 30, into the tissue 16, and uses differences in the time delay between highly scattered and minimally scattered photons included in the composite reflected signal 20. Light that travels the most direct path, identified as ballistic light 22, between the transmitter and receiver will arrive first, and photons that propagate along longer paths due to multiple scattering identified as snake and diffuse light, 24 and 26, respectively, will arrive at progressively later times. The ballistic light 22 is identified in the received section 14 of FIG. 1(A) as contained in the smaller signal 34, whereas the multiple scattered light 24 and 26 are identified in the received section of FIG. 1(A) as contained in the larger signal 32.
The time domain approach of FIG. 1(A) uses a high speed shutter, generally identified by reference number 36, that is opened for a short time to allow only the early photons associated with the ballistic light 22 to be detected and is then closed to leave out the multiply scattered, delayed photons associated with the multiple scattered light 24 and 26. One associated approach uses a streak camera receiver, which is capable of very short (picosecond) gate times and dynamic ranges on the order of 104 and is disclosed in the technical article of B. B. Das, D. M. Yoo, R. R. Alfano, entitled “Ultrafast Time-Gates Imaging in Thick Tissues: A Step Toward Optical Mammography,” published in Optics Letters, vol. 18, pp. 1092–1094, Jul. 1993. An additional approach is disclosed in the technical article of D. J. Hall, J. C. Hebden, D. T. Delphy, entitled “Imaging Very-Low-Contrast Objects in Breastlike Scattering Media with a Time-Resolved Method,” published in Applied Optics, vol. 36, pp. 7270–7276, October 1997. Other related techniques use nonlinear mixing of the received pulse and the delayed transmitted pulse to perform the temporal discrimination, such as that disclosed in the technical article of Bashkansky and J. Reintjes, entitled “Nonlinear-Optical Field CrossCorrelation Techniques for Medical Imaging with Lasers,” published in Applied Optics, vol. 32, pp. 3842–3845, July 1993, as well as another approach disclosed in the technical article of F. Liu, K. M. Yoo, R. R. Alfano, entitled “Ultrafast Laser-Pulse Transmission and Imaging Through Biological Tissues,” published in Applied Optics, vol. 32, pp. 554–558, February 1993. The main disadvantage of the time-gated operations included in the time domain approach is that the receiver bandwidth must be large to recover the short transmitted pulse. This increases system complexity and receiver noise.
The coherence domain approach (FIG. 1(B)), transmits a burst of light 38 in the direction 40 into the tissue 16 and uses coherent gate devices, associated with the received section 14, which rely on optical interference between the image-bearing photons (contained in the scattered signal 42). The multiply scattered light consisting of a component 46 associated with the snake light 24 and a component 48 associated with the diffuse light 26 becomes uncorrelated with the transmitted light and does not produce an interference signal. One such coherence approach is more fully described in the technical article of J. A. Izatt, M. D. Kulkarni, K. Kobayashi, M. V. Sivak, J. K. Barton, and A. J. Welsch, entitled “Optical Coherence Tomography for Biodiagnostics,” published in Optics and Photonics News, vol. 8, pp. 41–47, 1997, whereas another such coherence approach is disclosed by M. R. Hee, J. A. Izatt, J. M. Jacobson, and J. G. Fujimoto, in the technical article entitled “Femtosecond Transillumination Optical Coherence Tomography,” published in Optics Letters, vol. 18, pp. 950–952, 1993. A further related article is disclosed by A. F. Fercher, entitled “Optical Coherence Tomography,” published in Journal of Biomedical Optics, vol. 1, no. 2, pp. 157–173, April 1996.
In the coherence domain approach of FIG. 1(B), optical interference occurs only for photons that are coherent with the reference signal. More particularly, optical interference occurs only between signals 38 and 42. Therefore, diffuse, incoherent photons associated with snake light 24 and diffused light 26 are gated out in this approach. Since the length of the gate opening is determined by the coherence length of the reference pulse 38, very short coherence length sources, such as light emitting diodes, are being investigated for use in this technique. Although micrometer resolution of suspected tumors is possible with this technique, the penetration depth to encompass the target 16 is limited to 1–2 mm due to the high degree of optical scattering and subsequent loss of optical coherence.
The frequency domain approach (FIG. 1(C)) is a variation of the time domain method of FIG. 1(A). The frequency domain approach of FIG. 1(C) transmits a signal 50 in the direction 52 into the tissue 16 and uses phase 54 and amplitude 56 measurements associated with the received section 14 to measure the relationship between the ballistic light 22, snake light 24, and diffused light 26, all shown in FIG. 1(C) in the received section 14.
Since the time and frequency domains of the associated transmitted and reflected signals are related through Fourier transforms, approaches similar to the time gating technique can be used in the frequency domain approach. While the time domain approach uses amplitude and time to discriminate multiply scattered, diffuse photons of light from the more direct snake and ballistic photons of light, the frequency domain uses the differences in the amplitude 56 and phase 54 of a modulated optical signal to perform this task.
Since the majority of photons are scattered many times while traversing a very turbid medium, such as that of tissues, previous work has focused on low frequency (<1 GHz) modulation of signal 50 and diffusely scattered light to detect imbedded objects, such as tumors in tissues. One such approach is disclosed in the technical article of M. A. O′Leary, D. A. Boas, B. Chance, A. G. Yodh, entitled “Experimental Images of Heterogeneous Turbid Media by Frequency-Domain Diffusing-Photon Tomography,” published in Optics Letters, Vol. 20, pp. 426–428, 1995. Further, U.S. Pat. Nos. 6,064,917, 5,917,190, 5,424,843 describe features associated with the frequency domain approach.
The benefits of this frequency domain approach include reduced system complexity and receiver bandwidth. Furthermore, the absorption and scattering properties of the tissue can be calculated through use of diffusion equations and the measured amplitude and phase information. The main disadvantage is that an extremely precise measurement of the phase associated with the transmitted and reflected signals is required to achieve high depth resolution of possible tumors at these low (<1 GHz) modulation frequencies. The other disadvantage is that at these low modulation frequencies, the signal is dominated by diffuse photons that severely degrade the image quality. It is desired to provide a system for detecting the presence of cancerous tumors in tissues that does not suffer the drawbacks of the systems of FIGS. 1(A), 1(B), and 1(C).